A concise synthesis of β-sitosterol and other phytosterols

A convenient synthesis of sidechain-modified phytosterols is achieved via a temporary masking of the stigmasterol 5,6-alkene as an epoxide. Following performance of the desired modification, the alkene is regenerated through a mild deoxygenation. The approach is applied to the syntheses of β-sitosterol and campesterol acetate, and suggests a facile route to the (Z)-isomers of Δ22–23 phytosterols. Includes Supplementary Data

Stereoselective allylation of chiral monoperoxyacetals

Neighboring iodo-, alkoxy-, acetoxy- and silyl groups impart useful levels of diastereoselection in the Lewis acid-mediated allylation of monoperoxyacetals. Although monoperoxyacetals are found to be considerably less reactive than corresponding nonperoxidic acetals, similar stereochemical trends are observed in the two series

DECOMPOSITION OF ORGANIC PEROXIDES AND HYDROGEN PEROXIDE BY THE IRON THIOLATES AND RELATED COMPLEXES

Disclosed herein is a method of reducing or disproportionating peroxide, comprising combining an organic chalcogenide, an iron salt, and the peroxide in the presence of an additional reductant, which can be the organic chalcogenide. The method can be used to, e.g., prepare alcohols from peroxides and to disproportionate hydrogen peroxide into water and oxygen

A click-based modular approach to introduction of peroxides onto molecules and nanostructures

Copper-promoted azide/alkyne cycloadditions (CuAAC) are explored as a tool for modular introduction of peroxides onto molecules and nanomaterials. Dialkyl peroxide-substituted alkynes undergo Cu(I)- promoted reaction with azides in either organic or biphasic media to furnish peroxide-substituted 1,2,3- triazoles. Heterolytic fragmentation of the peroxide to an aldehyde, a side reaction that appears to be related to the formation of the triazole, can be suppressed by use of excess alkyne, the presence of triethylsilane, or by use of iodoalkyne substrates. Complementary reactions of simple alkynes with azidosubstituted peroxides are much less efficient. Click reactions of alkynyl peroxyacetals are also reported; reductive fragmentation can be minimized by increasing the distance between the peroxyacetal and the alkyne. The strategy enables modular introduction of dialkyl peroxides and peroxyacetals onto gold nanoparticles, the first such process to be reported

Tandem application of C-C bond-forming reactions with reductive ozonolysis

Several variants of reductive ozonolysis, defined here as the in situ generation of aldehydes or ketones during ozonolytic cleavage of alkenes, are demonstrated to work effectively in tandem with a number of C-C bond-forming reactions. For reactions involving basic nucleophiles (1,2- addition of Grignard reagents, Wittig or Horner-Emmons olefinations, and directed Aldol reactions of lithium enolates) the one-pot process offers a rapid and high-yielding alternative to traditional two-step protocols

B(C\u3csub\u3e6\u3c/sub\u3eF\u3csub\u3e5\u3c/sub\u3e)\u3csub\u3e3\u3c/sub\u3e-promoted tandem silylation and intramolecular hydrosilylation: diastereoselective synthesis of oxasilinanes and oxasilepanes

B(C6F5)3 promotes regio- and stereoselective cyclizations of unsaturated alkoxysilanes to generate oxasilinanes and oxasilepanes. The same products are available directly from alkenols via tandem silylation and hydrosilylation

Synthesis Of Alkyl Hydroperoxides Via Alkylation Of \u3ci\u3egem\u3c/i\u3e-Dihydroperoxides

Two-fold alkylation of 1,1-dihydroperoxides, followed by hydrolysis of the resulting bisperoxyacetals, provides a convenient method for synthesis of primary and secondary alkyl hydroperoxides

Approaches to the Total Synthesis of Aplysiatoxin

Approaches to the synthesis of the polyacetate tumor promoter aplysiatoxin (1a) are described. The spiroketal framework was convergently constructed in a heteroatom Diels-Alder cyclization to afford spiroketal 11. The desired spirocenter stereochemistry was achieved, in a key reaction pitting steric strain against the anomeric effect, by acid-catalyzed isomerization of spiroketal 12 to spiroketal13. Subsequent manipulation furnished alcohols 16A and 16B, which were the starting materials for investigations into macrocyclization and introduction of the C-3 lactol. 16A and 16B were efficiently converted to macrolactones 23A and 23B. The macrolactones were deprotected and brominated to furnish 27A and 27B, representing both possible C-15 epimers of 3-desoxyaplysiatoxin methyl ether. Attempted removal of the phenol methyl ether proved impossible. Nuclear Overhauser effect difference spectra on 27B showed signal enhancements within the rigid spiroketal framework analogous to those observed in derivatives of the natural product. Attempted transannular remote oxidation of C-3 using a C-9 alkoxy radical derived from the nitrite ester of 16B afforded, as the predominant product, the C-9 ketone resulting from fragmentation of the initial alkoxy radical; an alternate route involving allylic oxidation of the C-3 hydroxyethyl sidechain of 16A or 16B also failed to functionalize the C-3 position. Circular dichroism (CD) spectra of 16A and 16B imply that alcohol 16B contains the natural (S) stereochemistry at the C-15 methyl ether. [Chemical structures 1a, 11, 12, 13, 16A, 16B, 23A, 23B, 27A, and 27B. See abstract in scanned thesis for details.]</p

β-Keto and β-hydroxyphosphonate analogs of biotin-5’-AMP are inhibitors of holocarboxylase synthetase

Holocarboxylase synthetase (HLCS) catalyzes the covalent attachment of biotin to cytoplasmic and mitochondrial carboxylases, nuclear histones, and over a hundred human proteins. Nonhydrolyzable ketophosphonate (β-ketoP) and hydroxyphosphonate (β-hydroxyP) analogs of biotin-5′-AMP inhibit holocarboxylase synthetase (HLCS) with IC50 values of 39.7 μM and 203.7 μM. By comparison, an IC50 value of 7 μM was observed with the previously reported biotinol-5\u27-AMP. The Ki values, 3.4 μM and 17.3 μM, respectively, are consistent with the IC50 results, and close to the Ki obtained for biotinol-5\u27-AMP (7 μM). The β-ketoP and β-hydroxyP molecules are competitive inhibitors of HLCS while biotinol-5\u27-AMP inhibited HLCS by a mixed mechanism

β-Keto and β-hydroxyphosphonate analogs of biotin-5’-AMP are inhibitors of holocarboxylase synthetase

Holocarboxylase synthetase (HLCS) catalyzes the covalent attachment of biotin to cytoplasmic and mitochondrial carboxylases, nuclear histones, and over a hundred human proteins. Nonhydrolyzable ketophosphonate (β-ketoP) and hydroxyphosphonate (β-hydroxyP) analogs of biotin-5′-AMP inhibit holocarboxylase synthetase (HLCS) with IC50 values of 39.7 μM and 203.7 μM. By comparison, an IC50 value of 7 μM was observed with the previously reported biotinol-5\u27-AMP. The Ki values, 3.4 μM and 17.3 μM, respectively, are consistent with the IC50 results, and close to the Ki obtained for biotinol-5\u27-AMP (7 μM). The β-ketoP and β-hydroxyP molecules are competitive inhibitors of HLCS while biotinol-5\u27-AMP inhibited HLCS by a mixed mechanism